Experts agree that both genes and environmental factors contribute to development of autism with recent research suggesting a surprisingly strong role for environmental factors. However, which factors may play important roles remains elusive even though the public is very concerned about environmental influences. Ambient air pollution has recently been of growing concern for the prenatal and early life development of autism with alarming reports of positive associations from very few and mainly small studies. Our own recent pilot study of ~7,000 autistic children in LA, suggested increases in risk related to prenatal exposure to traffic albeit risks were much smaller in size than reported in previous studies (5). Taken together, findings from previous mostly small-scale studies raise an important public health issue and the necessity to conduct a large- scale population based investigation with state-of-the-science air pollution exposure assessment during vulnerable developmental periods to address the question whether and what type of air pollution poses a risk for autism. Should these results be confirmed in well-designed and large-scale studies, this would have critical implications for the protection of the fetus and for air pollution regulations. This propoal addresses this question in a timely and efficient manner. Here, we propose to thoroughly examine hypotheses that exposure to air pollution during vulnerable periods around conception, in utero, and in the first year of life increases risks of autism in children. We propose to use highly sophisticated modeling and analytical techniques for the detailed spatial and temporal assessment of air pollution, developed, validated, and established by our group. We propose to examine these exposures during vulnerable periods using for the first time, a statewide population based birth cohort of autistic disorder cases (>35,000) and controls (ratio 1:10). California (CA) is an excellent location for studying potential environmental contributions to autism. The CA Dept. of Developmental Services operates a statewide system that coordinates services for children with autism and maintains electronic records. Further, the state of CA has among the highest levels of air pollution in the nation and a dense air pollution monitoring network. The goal of this proposal is thus to explore - for the first time - reliably and comprehensibly possible effects of air pollution during susceptible developmental periods and the risk of autism based on a statewide population in CA, using highly sophisticated state-of-the-science air pollution exposure assessment and cutting edge analytical approaches. This will help to elucidate whether or not, this ubiquitous environmental exposure contributes to the risk of autism in children. Should this association be shown to exist in this large-scale high quality study, it would provide the necessary evidence for preventive environmental policies to protect the developing child and thus provide a unique opportunity for population based prevention of autism.